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Research Team Works On Genetic Test For BRD Susceptibility

A team of researchers is making headway in genetic testing of cattle for susceptibility to bovine respiratory disease (BRD). Success could have far-reaching implications on producers and society.

By Heather Smith Thomas | Oct 05, 2013

Bovine respiratory disease (BRD), also known as pneumonia or shipping fever, is the most costly disease in the U.S. cattle industry, particularly for the feedlot sector. More than 1 million animals are lost each year to BRD, at an estimated price tag of more than $1 billion.

There’s hope on the horizon for prevention of BRD, however. Today’s genetic selection tools are allowing researchers to investigate — and hopefully find — genetic approaches to select for cattle less susceptible to this disease complex.

In fact, several research groups are working together on the Bovine Respiratory Disease Complex (BRDC) Coordinated Agricultural Project (CAP). These CAPs are awarded USDA grants to promote collaboration, communication and the exchange of information among individuals, institutions, states and regions. The BRDC project involves researchers at Texas A&M University (TAMU); Washington State University (WSU); University of California, Davis (UC Davis); New Mexico State University, (NMSU); Colorado State University (CSU); University of Missouri (MU); USDA’s Agricultural Research Service; and Gene Seek Inc. of Lincoln, NE.

A five-year project

Now in its third year, this five-year CAP began by looking at 2,000 dairy calves (half as BRD cases and half as controls), and 2,000 feedlot animals (BRD cases and controls), to determine if genetic differences exist — genotyping them with a high-density single-nucleotide polymorphism (SNP) chip. The next step is validating the findings by using genotypes from an additional 1,000 dairy and 1,000 beef case/control animals from different geographic locations. It’s hoped the research leads to genetic tests to identify animals either resistant or susceptible to BRD.

“The science being done here in Texas is mainly data analysis,” says Womack, whose group oversees the project. Most of the animals for the study were collected in California, Colorado and New Mexico.

Neibergs says multiple projects are progressing simultaneously. “I try to keep everyone in the loop as we figure out which things work and which things don’t, and all the adjustments,” she adds.

Genetic differences

Blood samples are taken for genotyping, along with diagnostic swabs from nasal passages. The blood samples are processed at WSU, while diagnostic samples are split and sent to labs at UC Davis or WSU.

“From the blood, we extract DNA and keep the white blood cells in long-term storage. We split all samples and have backup samples at MU in case something happens to one of our facilities. We have data for each sample, such as the animal’s identification, age and diagnostics,” Neibergs says.

The DNA is extracted and sent for genotyping to GeneSeek®. “GeneSeek provides us with genotype data on 780,000 genetic variants for each animal. For 6,000 animals, times 780,000, this is a lot of variants. We conduct genetic analysis of those genotypes at WSU,” she adds.

MU’s Jerry Taylor and TAMU’s Christopher Seabury also analyze the samples, but use a slightly different approach. “If we get the same results, we’re more confident in our identification of the genomic regions associated with susceptibility to BRD,” Neibergs explains.

The first set of nearly 3,000 dairy cattle has been completed, while the beef side is well underway, utilizing a feedyard in Colorado, she adds.

“We’ll end up with 2,000 feedlot samples and another 1,000 samples from a Grow-Safe system, which allows measurement of individual feed intake. We’ll have individual data on all the animals that get sick, and those that don’t. We can compare differences in weight gained between the sick and healthy animals, treatment costs — and how many didn’t recover.”

Neibergs says these data will provide a good estimate on BRD’s actual cost to a feedlot operation, and how illness affects animals’ ultimate performance. The cattle will be followed through the processing plant to assess how BRD affects carcass weight, yield and quality. Economic losses through the feedlot and processing will be calculated.

“This will tell us how much a producer can invest to prevent BRD, and what premiums could be passed to cow-calf producers and stocker operations to have BRD-resistant cattle,” Neibergs says.

But breeding for animals less susceptible to BRD is just one component of preventing BRD. Animal selection must be done in conjunction with best management practices, Neibergs adds. Economic analyses will determine the breakeven spending limit on breeding, health and preconditioning programs.

Womack’s team at TAMU is looking at copy number variation in the genes. “We’re looking at one particular type of variation that occurs in genomes. These are called SNPs. Another type of variation more recently discovered is the copy number variations [CNVs],” Womack says.

The heart and soul of this project is the SNP assay, looking at the big SNP chips with thousands of variants over several thousand cattle, Taylor says.

“The smaller part is being done here, looking at CNVs. We’re screening the whole genome to find the important differences between animals that get sick and animals that don’t.” Eventually, he says, this will lead to discovery of the genes responsible. And that could lead to genetic tests aiding in selection, new vaccines, new diagnostics, new treatments, etc., to reduce BRD.

Selection tool

This exciting new field will eventually provide tools for selecting breeding stock. It also may help answer questions breeders have regarding the tendency for certain animals to be hardier and more disease-resistant than others.

There may be breed differences, variations within a breed, and some appreciable differences in crossbred animals. Heterosis tends to boost hardiness and decrease susceptibility to disease.

The gene pool is diminished when a breed is established, selecting animals for certain traits and then breeding those animals to one another with no outcrosses. This is done to “stack” genetics so the animals always breed true, but it also narrows the genetic possibilities — including possibilities for maximum disease resistance.

“We know disease resistance [and fertility] has relatively low heritability — around 10%,” Van Eenennaam explains. “When a trait has low heritability, it’s hard to improve on it from within-breed selections. Low-heritability traits are the ones that benefit most from heterosis. Thus, it stands to reason that crossbreeding would be beneficial for improving disease resistance. We certainly see this in terms of the overall health of crossbred animals,” she says.

Womack says the group’s studies will allow it to get closer to the reasons. “We’ve known for a long time that there is some heritability to disease resistance, but it’s been hard to get a finger on where and what the genes are,” he says.

Van Eenennaam says genetic selection starts with the cow-calf producer. While the feedlot industry is most dramatically affected by BRD, the cattle coming in are selected and bred by the cow-calf sector. It makes sense that ranches with a good track record for health will have a better market for their calves.

“If we can identify markers, and people start putting this into their selection decisions when breeding cattle, feedlots will prefer to buy those animals,” she says.

Better diagnosis and treatment

Another component of the project consists of studying the pathogens — both bacteria and viruses — that researchers find in the test cattle, Womack says.

“There are six major pathogens associated with BRD. We don’t know which cause the disease and which tag along as opportunists to make things worse. We’re looking at these, and for unknown pathogens that may be hiding there somewhere,” he says.

Researchers want to determine if BRD in different parts of the country and different environments might originate with a different pathogen or set of pathogens. “Hopefully, we’ll come up with ways to help diagnose sick animals early, to determine which pathogens are there, and how they should be treated,” Womack says. Such information may lessen the dependence on antibiotic use in food animals.

The researchers emphasize that feedlot death losses from BRD, and its treatment costs, are huge expenses. It’s estimated that 10% of animals in feedlots will acquire BRD. “All those cattle — not just those that die — become a liability. They go off feed and have reduced weight gain,” Womack says. Profit on those animals drops dramatically; they take longer to get to finish weight, plus the treatment expense.

“If we can do more prevention, we won’t have to worry as much about antibiotic resistance, nor the high costs of treating the animals,” Neibergs says.

Genetic tests

The ultimate goal of the Bovine Respiratory Disease Complex Coordinated Agricultural Project is to develop genetic tests to enable producers to determine which animals might have more (or less) disease resistance. “We first need to validate these tests and make sure they actually work. We don’t know if these will be powerful enough to work well in multiple breeds, but that is our ultimate goal,” says Allison Van Eenennaam, University of California, Davis.

The beef project will be more challenging than dairy because there are more breeds involved, she says.

“We’ve found that a test that works well in one breed, like the Angus 50K from Zoetis, doesn’t work well in Herefords, for example. We’re hoping, since we are using the high-density 770,000 chip, that it will help with this, and identify markers that work well across breeds,” she adds.

Van Eenennaam is confident DNA testing is coming, and the price will drop. “It will probably be done on a larger scale because it can give us multiple pieces of information. If we can include disease resistance information, this would be an additional value from a DNA test besides parentage, genetic defects, genetic merit estimates for various production traits, etc.,” she says.

Van Eenennaam says the project is looking to develop education materials for different sectors of the industry, with recommended management approaches to help minimize disease.

“The cow-calf producer plays a huge role in delivering animals to the feedlot to maximize their chances of a disease-free stint. There are usually some financial rewards, if the feedlot recognizes a producer is doing a good job,” she says.

Sifting the data

The project is generating millions of pieces of information. “We’re looking for genome-wide association studies. We look for consistent associations of a particular part of a genome. Hopefully, this will lead us to the genes responsible for the disease,” says Texas A&M University’s Jim Womack.

“The chips themselves may be useful for selective breeding of disease-resistant animals. These single-nucleotide polymorphisms [SNPs] are markers, and we can get as many as 800,000 of these on a single chip. The goal is to be able to tell from the markers which animals are resistant and which are susceptible to disease.

“Right now, we’re just looking at sick animals and comparing them with healthy animals, looking to find variances consistently associated with the sick or the well animals. Our preliminary data looks very promising, though it will be awhile before we start releasing data to the public,” Womack says.

Heather Smith Thomas is a rancher and freelance writer based in Salmon, ID.